Corneal collagen crosslinking (CXL) is an effective method to halt the disease progression of keratoconus, a progressive corneal dystrophy leading to cone shaped cornea. Despite the efficacy of standard protocol, the concerning step of this procedure is epithelial debridement performed to facilitate the entry of riboflavin drug. Riboflavin, a key molecule in CXL protocol, is a sparsely permeable hydrophilic drug in corneal tissues.
View Article and Find Full Text PDFBiochim Biophys Acta Biomembr
February 2024
Cell penetrating peptides (CPP) with their intrinsic ability to penetrate plasma membranes facilitate intracellular uptake of various macromolecules. Although a substantial number of CPPs have been reported over the last three decades, the number is still inadequate when compared to the theoretically feasible peptides with similar physicochemical composition. Marine organisms, due to their hostile environment, are an immense source of several high-valued therapeutically relevant peptides.
View Article and Find Full Text PDFThe RNA-dependent RNA polymerase (RdRp) complex of SARS-CoV-2 lies at the core of its replication and transcription processes. The interfaces between holo-RdRp subunits are highly conserved, facilitating the design of inhibitors with high affinity for the interaction interface hotspots. We, therefore, take this as a model protein complex for the application of a structural bioinformatics protocol to design peptides that inhibit RdRp complexation by preferential binding at the interface of its core subunit nonstructural protein, nsp12, with accessory factor nsp7.
View Article and Find Full Text PDFEffective delivery of drug molecules to the target site is a challenging task. In the last decade, several innovations in the drug delivery system (DDS) have tremendously improved the therapeutic efficacy of drug molecules. Among various DDS, cell-penetrating peptides (CPPs) based DDS have gathered notable attention owing to their safety, efficacy, selectivity, specificity, and ease of synthesis.
View Article and Find Full Text PDFWe investigate the role of Tachyplesin (Tpl), a marine antimicrobial cell-penetrating peptide, as an anti-HBV agent. Our findings, using confocal microscopy and flow cytometry, demonstrate the internalization of FITC-Tpl in both Huh7 and HepG2 cell lines. Further, our results show that Tpl inhibits the expression of HBV proteins, including hepatitis B surface antigen (HBsAg) and hepatitis B 'e' antigen (HBeAg) in cell supernatants of human liver cell lines transfected with 1.
View Article and Find Full Text PDFVisceral leishmaniasis (VL) is among the most neglected tropical diseases in the world. Drug cell permeability is essential for killing the intracellular residing parasites responsible for VL, making cell-permeating peptides a logical choice to address VL. Unfortunately, the limited biological stability of peptides restricts their usage.
View Article and Find Full Text PDFAppl Microbiol Biotechnol
August 2022
Reports on chloroplast-targeted protein delivery using cell-penetrating peptides are scarce. In this study, a novel peptide-based macromolecule delivery strategy targeting chloroplasts was successfully developed in wheat mesophyll protoplasts. A peptide derived from the signal sequence of the chloroplast-targeted protein of ferredoxin-thioredoxin reductase catalytic chain of Spinacia oleracea with UniProtKB Id-P41348 exhibits properties of cellular internalization.
View Article and Find Full Text PDFBiochim Biophys Acta Biomembr
July 2022
Mycobacterium tuberculosis is an etiological agent of tuberculosis (TB) known to be a highly contagious disease and is the major cause of mortality from a single infectious agent worldwide. Emergence of multi-drug resistant and extremely drug resistant strains of M. tuberculosis has made TB management extremely challenging eliciting the urgent need for alternative therapeutics.
View Article and Find Full Text PDFA group of seven peptides from spider venom with diverse sequences constitute the latarcin family. They have been described as membrane-active antibiotics, but their lipid interactions have not yet been addressed. Using circular dichroism and solid-state N-NMR, we systematically characterized and compared the conformation and helix alignment of all seven peptides in their membrane-bound state.
View Article and Find Full Text PDFDelivery of therapeutics to the ocular tissues is challenging due to various anatomical and physiological barriers imposed. Cell penetrating peptides (CPPs) have emerged as potent drug nanocarriers that have been shown to overcome these barriers and enhance bioavailability of therapeutic macromolecules in deep ocular tissues. In the present study, an ocular targeting CPP has been designed by exploring potential targets of anterior ocular tissues in particular receptors, transporters and glycosaminoglycans (GAGs).
View Article and Find Full Text PDFBiochim Biophys Acta Biomembr
August 2021
Visceral leishmaniasis is one of the neglected tropical diseases caused by an intracellular parasite, Leishmania donovani. Drug resistance, adverse side effects and long treatment regimes are important limitations in achieving the effective elimination of visceral leishmaniasis. In the absence of any vaccine, chemotherapy remains a viable treatment for leishmaniasis.
View Article and Find Full Text PDFNatamycin is the only FDA approved drug that is used as a first line of treatment for fungal keratitis caused by filamentous fungi, however natamycin is known for poor corneal penetration. Cell penetrating peptides (CPPs) are emerging nanocarriers for the enhanced delivery of various macromolecules owing to their distinct cellular translocation ability. In the present study, tissue penetration ability and antifungal efficacy of CPP (Tat) conjugated natamycin has been investigated and compared with natamycin alone in vivo.
View Article and Find Full Text PDFCapsids of several RNA viruses are reported to have unconventional roles attributed to their subcellular trafficking property. The capsid of CHIKV is also found to localize in the nucleus, but the rationale is not yet clear. To understand the role of the nuclear-localized capsid, we examined the nucleic acid binding and cargo delivery activity of the CHIKV capsid.
View Article and Find Full Text PDFThe levels of microRNAs (miRNAs) are altered in various diseases including glioblastoma (GBM) and this alteration may have widespread effects on various hallmarks of cancer cells. MiR210 is overexpressed in GBM and functions as an oncogenic miRNA. Anti-miR210 therapy holds great promise but its efficient delivery remains a major challenge.
View Article and Find Full Text PDFEur J Pharm Sci
March 2018
Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) share certain physicochemical parameters such as amphipathicity, hydrophobicity, cationicity and pI, due to which these two groups of peptides also exhibit overlapping functional characteristics. In our current work, we have evaluated antimicrobial properties of cell-penetrating peptides derived from Latarcin1. Latarcin derived peptide (LDP) exhibited antimicrobial activity against representative microorganisms tested and bactericidal effect against methicillin resistant Staphylococcus aureus (MRSA), which was used as model organism of study in the present work.
View Article and Find Full Text PDFBiochim Biophys Acta Biomembr
February 2018
Cell-penetrating peptides and antimicrobial peptides share physicochemical characteristics and mechanisms of interaction with biological membranes, hence, termed as membrane active peptides. The present study aims at evaluating AMP activity of CPPs. LDP-NLS and LDP are Latarcin 1 derived cell-penetrating peptides and in the current study we have evaluated antifungal and cell-penetrating properties of these CPPs in Fusarium solani.
View Article and Find Full Text PDFCell-penetrating peptides are short cationic peptides with inherent ability to cross the plasma membrane barrier as well as intracellularly deliver cargo molecules conjugated to them. Venoms from snakes, scorpions and spiders are rich in membrane-active peptides. Crotamine from snake venom as well as maurocalcine and imperatoxin isolated from scorpion venoms have been reported to possess cell-penetrating property in mammalian cells.
View Article and Find Full Text PDFBiochim Biophys Acta Biomembr
February 2017
CyLoP-1 is a cysteine-rich cell-penetrating peptide derived from nuclear localization sequence of snake toxin, crotamine. The peptide has shown cytoplasmic uptake in mammalian cells at lower concentrations. In the present study, the cell-penetrating and antimicrobial activity of the peptide has been studied by employing mammalian cells, plant cells as well as bacterial and fungal pathogens.
View Article and Find Full Text PDFMarine organisms are known to be a rich and unique source of bioactive compounds as they are exposed to extreme conditions in the oceans. The present study is an attempt to briefly describe some of the important membrane-active peptides (MAPs) such as antimicrobial peptides (AMPs), cell-penetrating peptides (CPPs) and peptide toxins from marine organisms. Since both AMPs and CPPs play a role in membrane perturbation and exhibit interchangeable role, they can speculatively fall under the broad umbrella of MAPs.
View Article and Find Full Text PDFMembrane-active peptides can be classified as cell-penetrating peptides and antimicrobial peptides (AMPs) that are known to play interchangeable roles. In this study, this dual behaviour was studied for the marine AMP, tachyplesin. It is a well-established cyclic peptide known to possess antimicrobial properties and was investigated for its cell-penetrating property and cargo delivery ability.
View Article and Find Full Text PDFPurpose: Enhancing the penetration ability of the antifungal drug natamycin, known to possess poor penetration ability through the corneal epithelium, by complexing with cell penetrating peptides.
Methods: The drug, natamycin was conjugated to a cell penetrating peptide, Tat-dimer (Tat2). The uptake ability of the conjugate in human corneal epithelial cells and its antifungal activity against filamentous fungi, F.
The emerging field of synthetic biology holds tremendous potential for developing novel drugs to treat various human conditions. The current study discusses the scope of synthetic biology for human therapeutics via microbial approach. In this context, synthetic biology aims at designing, engineering and building new microbial synthetic cells that do not pre-exist in nature as well as re-engineer existing microbes for synthesis of therapeutic products.
View Article and Find Full Text PDFThe global sustainable bioenergy (GSB) project was formed in 2009 with the goal of providing guidance with respect to the feasibility and desirability of sustainable, bioenergy-intensive futures. Stage 1 of this project held conventions with a largely common format on each of the world's continents, was completed in 2010, and is described in this paper. Attended by over 400 persons, the five continental conventions featured presentations, breakout sessions, and drafting of resolutions that were unanimously passed by attendees.
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